(S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺 | 192726-05-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺
• 中文别名: 洛匹那韦EP杂质A
• 英文名称: (2S)-N-[(2S,4S,5S)-5-amino-4-hydroxy-1,6-diphenylhexane-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
• 英文别名: (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(2-oxotetrahydropyrimidin-2-yl)-3-methylbutanoyl)amino-1,6-diphenylhexane；(2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane；(S)-N-[(2S,4S,5S)-5-Amino-4-hydroxy-1,6-diphenylhexan-2-YL]-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-YL)butanamide；(2S)-N-[(2S,4S,5S)-5-amino-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
• CAS: 192726-05-9
• 化学式: C₂₇H₃₈N₄O₃
• 分子量: 466.624
• InChiKey: PSXHIAOZPOGORP-QORCZRPOSA-N

物化性质

• 沸点：
  762.2±60.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺 、 (2,6-二甲基苯氧基)乙酰氯 在 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 洛匹那韦
  参考文献：
  名称：

  Synthesis and Characterization of Novel Analogues of Lopinavir

  摘要：

  这项工作描述了四种洛匹那韦新颖类似物的鉴定、起源、合成、表征和控制，即洛匹那韦的亮氨酸类似物、异亮氨酸类似物、甲基类似物和二羟基类似物。

  DOI：

  10.14233/ajchem.2021.22954
• 作为产物：
  描述：

  (2S)-(1-四氢嘧啶-2-酮)-3-甲基丁酸 在 5%-palladium/activated carbon 、 甲酸铵 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 8.0h， 生成 (S)-N-[(2S,4S,5S)-5-氨基-4-羟基-1,6-二苯基己烷-2-基]-3-甲基-2-(2-氧代四氢嘧啶-1(2H)-基)丁酰胺
  参考文献：
  名称：

  Synthesis and Characterization of Novel Analogues of Lopinavir

  摘要：

  这项工作描述了四种洛匹那韦新颖类似物的鉴定、起源、合成、表征和控制，即洛匹那韦的亮氨酸类似物、异亮氨酸类似物、甲基类似物和二羟基类似物。

  DOI：

  10.14233/ajchem.2021.22954

文献信息

• Retroviral protease inhibiting compounds
  申请人：Abbott Laboratories

  公开号：EP1170289A2

  公开（公告）日：2002-01-09

  A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.

  披露了一种包含公式（II）取代基的化合物，作为一种HIV蛋白酶抑制剂。还披露了用于制造此类化合物的中间体以及制造此类中间体的过程。
• Processes and intermediates for preparing retroviral protease inhibitors
  申请人：Abbott Laboratories

  公开号：US06372905B1

  公开（公告）日：2002-04-16

  The instant invention provides processes and intermediates employed in the synthesis of ((2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)-amino-3-hydroxy-5-(2S-(1-tetrahydropyrimid-2-onyl)-3-methyl-butanoyl)amino-1,6-diphenylhexane and analogs thereof.

  本发明提供了用于合成((2S,3S,5S)-2-(2,6-二甲基苯氧乙酰)氨基-3-羟基-5-(2S-(1-四氢嘧啶-2-酰基)-3-甲基丁酰基)氨基-1,6-二苯基己烷及其类似物的过程和中间体。
• Design and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2‘ Ligands in Pseudosymmetric Dipeptide Isosteres
  作者：G. S. Kiran Kumar Reddy、Akbar Ali、Madhavi N. L. Nalam、Saima Ghafoor Anjum、Hong Cao、Robin S. Nathans、Celia A. Schiffer、Tariq M. Rana

  DOI：10.1021/jm070284z

  日期：2007.9.1

  A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure -activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.